Case Report: Durable, well-tolerated complete response to epcoritamab plus pirtobrutinib in Richter transformation relapsing after CD19 CAR T-cell therapy.

Abstract

Richter transformation (RT) that relapses after CD19-directed chimeric antigen receptor (CAR) T-cell therapy has no established therapy and carries a dismal prognosis. We report an 84-year-old man with multiply relapsed, biopsy-proven diffuse large B-cell lymphoma-type RT and a high-risk MYC/BCL2 double-expressor phenotype who developed systemic relapse, with extensive osteolytic bone disease, after lisocabtagene maraleucel. Three cycles of atezolizumab produced no objective benefit. Treatment with epcoritamab, a CD3xCD20 bispecific antibody, plus pirtobrutinib, a non-covalent Bruton tyrosine kinase inhibitor, produced complete nodal metabolic resolution within 3 months that deepened to a complete metabolic response (Deauville score 2) by 10 treatment cycles, with resolution of two interim osteolytic lesions whose transient nature illustrates the interpretive challenges of PET/CT response assessment after cellular and T-cell-engaging therapies. The chemotherapy-free regimen was well tolerated at age 84, with no cytokine release syndrome, no neurotoxicity, and no cytopenias; the only toxicity was mild, reversible dexamethasone-related myopathy. The patient remains in ongoing clinical remission after approximately 10 months of therapy. This case extends the reported experience with epcoritamab plus pirtobrutinib specifically to the post-CAR T-cell relapse setting and suggests that this chemotherapy-free doublet may warrant consideration as a salvage strategy for older or frail patients with RT who are unfit for further cytotoxic therapy.